Craniofacial bone regeneration using iPS cell-derived neural crest like cells

Kazuko Kikuchi, Tomoyuki Masuda, Naoki Fujiwara, Akiyoshi Kuji, Hiroyuki Miura, Han Sung Jung, Hidemitsu Harada, Keishi Otsu

Research output: Contribution to journalArticle

Abstract

Induced pluripotent stem (iPS) cells represent a powerful source for cell-based tissue regeneration because they are patient-specific cells and can differentiate into specialized cell types. Previously, we have demonstrated the derivation of neural crest like cells from iPS cells (iPS-NCLCs), and these cells have the potential to differentiate into dental mesenchymal cells, which subsequently differentiate into odontoblasts and dental pulp cells. In this study, we show that iPS-NCLCs can differentiate into mesenchymal stem cells (iPS-NCLC-MSCs), which contribute to craniofacial bone regeneration. iPS-NCLCs were cultured in serum-containing media and differentiated into functional MSCs, as confirmed by expression MSC markers and their ability to differentiate into osteoblasts, adipocytes, and chondrocytes in vitro. iPSNCLC- MSCs were negative for markers of undifferentiated iPS cells and did not develop into teratomas when transplanted to immunodeficient mice. Further, iPS-NCLC-MSCs grew normally and differentiated into osteoblasts on hydroxyapatite scaffolds in vitro. To assess the potential of iPS-NCLC-MSCs to regenerate craniofacial bone in vivo, iPS-NCLC-MSCs were transplanted into critical-size calvarial defects in immunodeficient mice for 8 weeks. Histological analysis revealed that iPS-NCLC-MSCs differentiated into osteoblasts and contributed to bone regeneration without tumor formation. These results indicate that iPS-NCLC-MSCs could be a potential candidate for cell-based craniofacial bone tissue repair and regeneration.

Original languageEnglish
Pages (from-to)1-10
Number of pages10
JournalJournal of Hard Tissue Biology
Volume27
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

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All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Biochemistry
  • Biomaterials
  • Orthopedics and Sports Medicine
  • Dentistry(all)
  • Cell Biology

Cite this

Kikuchi, K., Masuda, T., Fujiwara, N., Kuji, A., Miura, H., Jung, H. S., Harada, H., & Otsu, K. (2018). Craniofacial bone regeneration using iPS cell-derived neural crest like cells. Journal of Hard Tissue Biology, 27(1), 1-10. https://doi.org/10.2485/jhtb.27.1